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Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

  • Authors:
    • Xintong Lv
    • Feng Guo
    • Xiaoxue Xu
    • Zaixing Chen
    • Xuefei Sun
    • Dongyu Min
    • Yonggang Cao
    • Xianbao Shi
    • Lei Wang
    • Tianbao Chen
    • Chris Shaw
    • Huiling Gao
    • Liying Hao
    • Jiqun Cai
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Molecular Therapeutics Research Group, School of Pharmacy, Queen's University, Belfast BT7 1NN, United Kingdom, College of Life and Health Sciences, Northeastern University, Shenyang, Liaoning 110001, P.R. China
    Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6663-6671
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    Published online on: August 18, 2015
       https://doi.org/10.3892/mmr.2015.4227
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Abstract

Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence‑like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+‑free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p‑CaMKII; Thr‑286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p‑CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p‑CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co‑localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+‑free solution.
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Copy and paste a formatted citation
Spandidos Publications style
Lv X, Guo F, Xu X, Chen Z, Sun X, Min D, Cao Y, Shi X, Wang L, Chen T, Chen T, et al: Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution. Mol Med Rep 12: 6663-6671, 2015.
APA
Lv, X., Guo, F., Xu, X., Chen, Z., Sun, X., Min, D. ... Cai, J. (2015). Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution. Molecular Medicine Reports, 12, 6663-6671. https://doi.org/10.3892/mmr.2015.4227
MLA
Lv, X., Guo, F., Xu, X., Chen, Z., Sun, X., Min, D., Cao, Y., Shi, X., Wang, L., Chen, T., Shaw, C., Gao, H., Hao, L., Cai, J."Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution". Molecular Medicine Reports 12.5 (2015): 6663-6671.
Chicago
Lv, X., Guo, F., Xu, X., Chen, Z., Sun, X., Min, D., Cao, Y., Shi, X., Wang, L., Chen, T., Shaw, C., Gao, H., Hao, L., Cai, J."Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution". Molecular Medicine Reports 12, no. 5 (2015): 6663-6671. https://doi.org/10.3892/mmr.2015.4227
Copy and paste a formatted citation
x
Spandidos Publications style
Lv X, Guo F, Xu X, Chen Z, Sun X, Min D, Cao Y, Shi X, Wang L, Chen T, Chen T, et al: Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution. Mol Med Rep 12: 6663-6671, 2015.
APA
Lv, X., Guo, F., Xu, X., Chen, Z., Sun, X., Min, D. ... Cai, J. (2015). Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution. Molecular Medicine Reports, 12, 6663-6671. https://doi.org/10.3892/mmr.2015.4227
MLA
Lv, X., Guo, F., Xu, X., Chen, Z., Sun, X., Min, D., Cao, Y., Shi, X., Wang, L., Chen, T., Shaw, C., Gao, H., Hao, L., Cai, J."Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution". Molecular Medicine Reports 12.5 (2015): 6663-6671.
Chicago
Lv, X., Guo, F., Xu, X., Chen, Z., Sun, X., Min, D., Cao, Y., Shi, X., Wang, L., Chen, T., Shaw, C., Gao, H., Hao, L., Cai, J."Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution". Molecular Medicine Reports 12, no. 5 (2015): 6663-6671. https://doi.org/10.3892/mmr.2015.4227
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